公开(公告)号：US20160229916A1

公开(公告)日：2016-08-11

申请号：US15136152

申请日：2016-04-22

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Sean STEVENS ,  Tammy T. HUANG ,  Joel H. MARTIN ,  Jeanette L. FAIRHURST ,  Ashique RAFIQUE ,  Eric SMITH ,  Kevin J. POBURSKY ,  Nicholas J. PAPADOPOULOS ,  James P. FANDL ,  Gang CHEN ,  Margaret KAROW

IPC: C07K16/28

CPC classification number: C07K16/2866 ,  A61K2039/505 ,  C07K2317/14 ,  C07K2317/21 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92

Abstract: A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a KD of about 500 pM or less and blocks IL-6 activity with an IC50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.

公开(公告)号：US20230130799A1

公开(公告)日：2023-04-27

申请号：US17936059

申请日：2022-09-28

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Robert BABB ,  Darya BURAKOV ,  Gang CHEN ,  James P. FANDL ,  Yu ZHAO

IPC: C07K16/46 ,  C07K16/00 ,  C12N15/90 ,  C12N15/85

Abstract: This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antigen-binding proteins including monospecific and bispecific antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing multiple expression-enhancing locus.

公开(公告)号：US20190233544A1

公开(公告)日：2019-08-01

申请号：US16095084

申请日：2017-04-20

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Robert BABB ,  Darya BURAKOV ,  Gang CHEN ,  James P. FANDL ,  Yu ZHAO

IPC: C07K16/46 ,  C07K16/00 ,  C12N15/85

CPC classification number: C07K16/468 ,  C07K16/00 ,  C12N15/85 ,  C12N15/907

Abstract: This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antigen-binding proteins including monospecific and bispecifc antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing multiple expression-enhancing locus.

公开(公告)号：US20140315249A1

公开(公告)日：2014-10-23

申请号：US14182863

申请日：2014-02-18

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Changlin DOU ,  Gang CHEN ,  James P. FANDL

IPC: C12N15/63 ,  C07K16/00

CPC classification number: C12N15/635 ,  A01K2217/05 ,  C07K16/00 ,  C07K2317/14 ,  C07K2317/21 ,  C07K2319/00 ,  C12N15/63 ,  C12N15/85 ,  C12N2830/00 ,  C12N2830/15 ,  C12N2830/42 ,  C12N2840/20 ,  C12P21/00

Abstract: Compositions and methods for the inducible expression of genes in eukaryotic cells are provided. Expression of a nucleotide sequence of interest encoding a protein of interest is controlled by a regulatory fusion protein that consists of a transcription blocking domain and a ligand-binding domain. When a cognate ligand for the ligand-binding domain is present, transcription of the nucleotide sequence of interest is blocked. Upon removal of the cognate ligand, the nucleotide sequence of interest is transcribed. The method is useful for large scale bioreactor production of a desired protein of interest in eukaryotic cells.

Abstract translation: 提供了在真核细胞中可诱导表达基因的组合物和方法。 通过由转录阻断结构域和配体结合结构域组成的调节融合蛋白来控制感兴趣的蛋白质的目标核苷酸序列的表达。 当存在配体结合结构域的同源配体时，感兴趣的核苷酸序列的转录被阻断。 去除同源配体后，转录目的核苷酸序列。 该方法可用于在真核细胞中大规模生物反应器生产期望的蛋白质。

公开(公告)号：US20240036043A1

公开(公告)日：2024-02-01

申请号：US18375755

申请日：2023-10-02

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Gang CHEN ,  Robert BABB ,  James P. FANDL

IPC: G01N33/569 ,  C07K16/00 ,  C07K16/22 ,  C07K16/32 ,  G01N33/50

CPC classification number: G01N33/56972 ,  C07K16/00 ,  C07K16/22 ,  C07K16/32 ,  G01N33/50 ,  C12N2510/02 ,  C07K2317/10 ,  C07K2317/92

Abstract: The present disclosure relates to a method for identifying cells that express antigen-specific antibodies with a high binding affinity for a monomeric antigen. Using fluorescence activated cell sorting, cells expressing high affinity antigen-specific antibodies are selected from a population of immune cells isolated from a mammal that has been immunized with or otherwise exposed to the antigen. Nucleic acids encoding the high affinity antibodies can then be cloned into other lymphoid and non-lymphoid cells where the antibody can be expressed and from which the antibodies can be secreted.

公开(公告)号：US20230322956A1

公开(公告)日：2023-10-12

申请号：US18054350

申请日：2022-11-10

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Robert BABB ,  Darya BURAKOV ,  Gang CHEN ,  James P. FANDL

IPC: C07K16/46 ,  C12N15/85 ,  C12N15/90 ,  C12Q1/6897 ,  C07K16/00

CPC classification number: C07K16/468 ,  C12N15/85 ,  C12N15/902 ,  C12Q1/6897 ,  C07K16/00 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/526 ,  C07K2317/565

Abstract: This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antibodies including bispecific antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing an expression-enhancing locus.

公开(公告)号：US20190263937A1

公开(公告)日：2019-08-29

申请号：US16095067

申请日：2017-04-20

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Robert BABB ,  Darya BURAKOV ,  Gang CHEN ,  James P. FANDL

IPC: C07K16/46 ,  C12N15/90 ,  C12N15/85 ,  C12Q1/6897

Abstract: This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antibodies including bispecifc antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing an expression-enhancing locus.

公开(公告)号：US20170327593A1

公开(公告)日：2017-11-16

申请号：US15526522

申请日：2015-11-13

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Gang CHEN ,  Robert BABB ,  James P. FANDL

IPC: C07K16/32 ,  G01N33/50 ,  C07K16/22 ,  C07K16/00

CPC classification number: C07K16/32 ,  C07K16/00 ,  C07K16/22 ,  C07K2317/10 ,  C07K2317/92 ,  C12N2510/02 ,  G01N33/50

Abstract: The present disclosure relates to a method for identifying cells that express antigen-specific antibodies with a high binding affinity for a monomeric antigen. Using fluorescence activated cell sorting, cells expressing high affinity antigen-specific antibodies are selected from a population of immune cells isolated from a mammal that has been immunized with or otherwise exposed to the antigen. Nucleic acids encoding the high affinity antibodies can then be cloned into other lymphoid and non-lymphoid cells where the antibody can be expressed and from which the antibodies can be secreted.